Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells

Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependen...

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Autores principales:	Ming-Feng Tsai, Shih-Ming Chen, Ann-Zhi Ong, Yi-Hsuan Chung, Pei-Ni Chen, Yi-Hsien Hsieh, Yu-Ting Kang, Li-Sung Hsu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	programed cell death shikonin reactive oxygen species renal cell carcinoma Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6ecef9c94dd64766896de539e606b5bd
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spelling	oai:doaj.org-article:6ecef9c94dd64766896de539e606b5bd2021-11-25T16:29:22ZShikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells10.3390/antiox101118312076-3921https://doaj.org/article/6ecef9c94dd64766896de539e606b5bd2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1831https://doaj.org/toc/2076-3921Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependently reduced the proliferation of Caki-1 and ACHN cells. Shikonin remarkably triggered necrosis and apoptosis in Caki-1 and ACHN cells in proportion to its concentration. Moreover, necrostatin-1 recovered cell viability in the presence of shikonin. Elevated ROS levels and mitochondrial dysfunction were also found in shikonin treatment groups. Pretreatment with N-acetyl cysteine remarkably mitigated shikonin-induced cell death and ROS generation. Western blot analysis revealed that shikonin reduced pro-PARP, pro-caspase-3, and Bcl-2 expression and increased cleavage PARP expression. Enhanced autophagy was also found in the shikonin-treated group as evidenced by acridine orange staining. Moreover, light chain 3B (LC3B)-II accumulation and enhanced p62 expression indicated that autophagy occurred in the shikonin-treated group. LC3B knockdown considerably recovered cell viability in the presence of shikonin. Shikonin treatment elevated p38 activity in a dose-dependent manner. In conclusion, our results revealed that shikonin triggered programmed cell death via the elevation of ROS level and p38 activity in different types of RCC cells. These findings suggested that shikonin may be a potential anti-RCC agent.Ming-Feng TsaiShih-Ming ChenAnn-Zhi OngYi-Hsuan ChungPei-Ni ChenYi-Hsien HsiehYu-Ting KangLi-Sung HsuMDPI AGarticleprogramed cell deathshikoninreactive oxygen speciesrenal cell carcinomaTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1831, p 1831 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	programed cell death shikonin reactive oxygen species renal cell carcinoma Therapeutics. Pharmacology RM1-950
spellingShingle	programed cell death shikonin reactive oxygen species renal cell carcinoma Therapeutics. Pharmacology RM1-950 Ming-Feng Tsai Shih-Ming Chen Ann-Zhi Ong Yi-Hsuan Chung Pei-Ni Chen Yi-Hsien Hsieh Yu-Ting Kang Li-Sung Hsu Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells
description	Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependently reduced the proliferation of Caki-1 and ACHN cells. Shikonin remarkably triggered necrosis and apoptosis in Caki-1 and ACHN cells in proportion to its concentration. Moreover, necrostatin-1 recovered cell viability in the presence of shikonin. Elevated ROS levels and mitochondrial dysfunction were also found in shikonin treatment groups. Pretreatment with N-acetyl cysteine remarkably mitigated shikonin-induced cell death and ROS generation. Western blot analysis revealed that shikonin reduced pro-PARP, pro-caspase-3, and Bcl-2 expression and increased cleavage PARP expression. Enhanced autophagy was also found in the shikonin-treated group as evidenced by acridine orange staining. Moreover, light chain 3B (LC3B)-II accumulation and enhanced p62 expression indicated that autophagy occurred in the shikonin-treated group. LC3B knockdown considerably recovered cell viability in the presence of shikonin. Shikonin treatment elevated p38 activity in a dose-dependent manner. In conclusion, our results revealed that shikonin triggered programmed cell death via the elevation of ROS level and p38 activity in different types of RCC cells. These findings suggested that shikonin may be a potential anti-RCC agent.
format	article
author	Ming-Feng Tsai Shih-Ming Chen Ann-Zhi Ong Yi-Hsuan Chung Pei-Ni Chen Yi-Hsien Hsieh Yu-Ting Kang Li-Sung Hsu
author_facet	Ming-Feng Tsai Shih-Ming Chen Ann-Zhi Ong Yi-Hsuan Chung Pei-Ni Chen Yi-Hsien Hsieh Yu-Ting Kang Li-Sung Hsu
author_sort	Ming-Feng Tsai
title	Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells
title_short	Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells
title_full	Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells
title_fullStr	Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells
title_full_unstemmed	Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells
title_sort	shikonin induced program cell death through generation of reactive oxygen species in renal cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6ecef9c94dd64766896de539e606b5bd
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_version_	1718413142790242304

Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells

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